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Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent

Rui Yamaguchi1, Takatoshi Yamamoto2, Arisa Sakamoto2

  • 1Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan; Graduate School of Medical Science, Kumamoto University Medical School, Kumamoto, Japan.

Blood Cells, Molecules & Diseases
|February 9, 2016
PubMed

Insights

Substance P (SP) enhances tissue factor (TF) release from macrophages, a key process in blood clotting. This release is mediated by the p22phox/β-arrestin 2/Rho A signaling pathway.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates procoagulant activity in macrophages.
  • Tissue factor (TF) is crucial for coagulation, and substance P (SP) is a pro-inflammatory neuropeptide involved in membrane bleb formation.

Purpose of the Study:

  • To investigate the role of substance P (SP) in regulating tissue factor (TF) release from GM-CSF-dependent macrophages.
  • To elucidate the signaling pathways involved in SP-mediated TF release.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) to quantify TF in cell lysates and supernatants.
  • Pharmacological inhibition of SP receptors, radical scavengers, and signaling pathway components (PKC, ROCK, dynamin, Akt).
  • Gene silencing using siRNA targeting p22phox, β-arrestin 2, and Rho A.

Main Results:

  • SP significantly decreased intracellular TF levels but increased TF in the culture supernatant of macrophages.
  • Aprepitant (SP/neurokinin 1 receptor antagonist) and pyrrolidinedithiocarbamate (radical scavenger) reduced SP-induced TF release.
  • Inhibitors of ROCK (Y-27632) and dynamin (dinasore), as well as siRNA targeting p22phox, β-arrestin 2, or Rho A, significantly blunted TF release.

Conclusions:

  • Substance P promotes the release of tissue factor from macrophages.
  • This process is regulated by the p22phox/β-arrestin 2/Rho A signaling pathway.
  • Visceral adipocytes were identified as a source of SP.
Keywords:
Granulocyte-macrophage colony-stimulating factorNeurokinin 1 receptorSubstance PTissue factor

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